The proposed research is a multifaceted approach to the basic pathogenesis of demyelinating disease. It will combine virologic, genetic, immunologic, morphologic, and biochemical methods in the study of the biology of demyelination. Studies will be conducted in animals, cells, and organ cultures and include the following: 1) Attempts to further characterize the chronic demyelination induced by the neurotropic strain of mouse hepatitis virus, JHM. The virus-cell interactions and host factors contributing to demyelination will also be investigated. 2) Examination of the long-term effect of acute and chronic viral infection on the blood brain barrier. In addition, attempts will be made to induce immunologically mediated demyelination across the blood brain barrier following viral infection. 3) Investigate the behavior and phagocytic properties of human glial cells in culture and their ability to become effectors of immune mediated demyelination.